Nucleolin-Targeting Aptamers for Selective Cancer Cell Sensitization
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Solution Overview
Problem
There is a need for new aptamers that can bind to and/or inhibit the nucleolin protein, which is overexpressed in many human tumors, to selectively sensitize cancer cells to DNA damaging agents.
Innovation Solution
Development of specific aptamers, including dimers, trimers, and tetramers, that have high sequence identity to specific sequences, which can bind to and inhibit the nucleolin protein, facilitating the delivery of agents to the nucleus of a cell and enhancing the sensitivity of cancer cells to ionizing radiation and chemotherapeutic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If aptamers are designed to bind to nucleolin protein, then cancer cell sensitivity to DNA damaging agents is improved, but selectivity between tumor cells and normal cells must be maintained
Solution Approach 1:
The aptamers are designed to specifically recognize and bind to nucleolin on the surface of tumor cells, which overexpress this protein. This localized targeting ensures that DNA damaging agents are sensitized primarily in tumor cells while normal cells with low nucleolin expression are spared, achieving selective cancer cell sensitization without widespread toxicity
Solution Approach 2:
The aptamers serve as intermediary molecules that bridge the DNA damaging agents and the nucleolin protein on tumor cell surfaces. By binding to nucleolin, the aptamers facilitate the delivery and action of DNA damaging agents specifically at the tumor site, acting as a targeted mediator that enhances therapeutic effect while minimizing off-target effects
2Measurement precision
If aptamer sequence identity is increased to improve binding specificity, then affinity for nucleolin is improved, but manufacturing complexity increases
Solution Approach 1:
The patent utilizes multiple copies of the aptamer sequence (dimers, trimers, tetramers) to enhance binding affinity and specificity for nucleolin. By repeating the aptamer motif, the system achieves higher precision in target recognition without requiring design of entirely new complex structures,而是 leveraging simplified repetitive units
Solution Approach 2:
The aptamer design is segmented into modular repeating units that can be independently synthesized and then assembled. This segmentation allows for standardized manufacturing of each unit with high sequence identity, while the overall complex is built from these simple, reproducible building blocks, reducing manufacturing complexity despite high binding specificity requirements
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The aptamers effectively sensitize cancer cells to ionizing radiation and chemotherapeutic agents, while sparing normal cells that do not express nucleolin on their surface, thereby improving cancer treatment outcomes.
Implementation Method 1
aptamers that can bind to and/or inhibit the nucleolin protein
Implementation Method 2
allowing more efficient tumor penetration while maintaining the ability to discriminate between proteins
Implementation Method 3
inhibition of nucleolin results in sensitization of cells to DNA damaging agents
Data Source
AI summary
Provided herein are compositions including aptamers capable of binding to and/or inhibiting the activity of nucleolin. Methods of treating cancer in a subject by administering such compositions are also provided.